2- Isoxazolines synthesis from oximes

A stereoselective synthesis of testosterone (261) was advanced by Fukumoto and co-workers (331), where ring B was joined to the C/D part by an intramolecular nitrile oxide cycloaddition. The key nitrile oxide dipole was generated in situ from oxime 258, which in turn was derived from the optically active tetrahydroin-danone 257. Tetracyclic isoxazoline (259) was obtained as a single stereoisomer... 

The concept of the use of dilithio reagents for the preparation of heterocyclic systems has been extended to the synthesis of 2-isoxazolin--5-ones10 by carboxylation of a dilithio oxime, followed by eyolin-zation, and the synthesis of pyrazoles from dilithiophenylhydrazones and trilithiothiohydrazones.11 12... 

In the seven-step stereoselective total synthesis of ptilocaulin 44 [21 ], a potent antileukemic and antimicrobial agent isolated [22] from marine sponges, the oxime 36 was treated with NaOCl providing the tricyclic isoxazoline 38 in 89% yield without isolation of the nitrile oxide intermediate 37 (Scheme 5) [23]. Isoxazoline 38 was obtained as a mixture of four diastereomers and their ratio was... 

The key step in the diastereoselective synthesis of model insect antifeedant 152 starting from a-cyclocitral 148 was the INOC reaction of oxime 149 or nitro alkane 150 to the isoxazoline 151 (Eq. 15) [42]. 

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

Intramolecular cycloaddition of the nitrile oxide intermediate generated from the unsaturated oxime 221 was used for an evenmal synthesis of la,2p,25-trihydroxy-vitamin D3 (262) (Scheme 6.90). Oxime 221, prepared from tri-O-isopropyhdene-d-mannitol (220), was processed as usual to give isoxazoline 222 in good yield and with excellent stereoselectivity. Conversion of 222 to the aldol 223 proceeded in the normal manner and further elaboration gave the desired diene intermediate 224 (262). 

This was demonstrated by Fukumoto and co-workers in a synthesis of (+)-albicanol (251), a sesquiterpene with potent hsh antifeedant properties (272,273). Oxime 248 [prepared from the (+)-Wieland-Miescher ketone 247] was subjected to cycloaddition using sodium hypochlorite and gave isoxazoline 249 in very good yield (Scheme 6.95). Conversion of 249 into (3-hydroxyketone 250 was again accomplished by the reductive hydrolysis sequence using Raney Ni and trimethyl... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

A -Isoxazolines exhibit considerable versatility in synthesis and one-pot oxidative ring contraction of stannyl oximes to A -isoxazolines with stereocontrol results from the strong directing effect of the tin group, followed by 1,3-dipolar cycloaddition (Scheme 26). In conjunction with other results, it was suggested that oximes with the stannyl group too far removed from the iminoxyl group (3-electton... 

Synthesis of 3-isoxazoline is accomplished only from quaternary salts oximation of flavyUum salts, nucleophilic attack on and basic treatment of 2-isoxazolium salts. Earlier literature on the synthesis of 3-isoxazoline is systematically comprehended <84CHEC-I(6)1,9IHC(49)i>. 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

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